Synthetic vascular prosthesis

ABSTRACT

A synthetic vascular prosthesis comprises a hollow tubular base member having a multitude of continuous pores and formed of an elastomer material, and a hydrogel layer formed on the inner surface of the base member. The hydrogel layer is partly embedded in the inner portion of the base member at the pores, thereby permitting anchoring adhesion between the hydrogel layer and the base member. A method for manufacturing the synthetic vascular prosthesis is also disclosed, in which the formation of pores in the base member is effected by two separate steps and the hydrogel layer is formed after formation of an inner porous portion of the base member.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a synthetic vascular prosthesis having anantithrombogenic hydrogel layer on the inner surface of the prosthesisand also to a method for manufacturing such a prosthesis.

2. Description of the Prior Art

Synthetic vascular prostheses that are currently in practical use areall of the neointima formation type, so that after implantation into aliving body, thrombi are immediately formed on the inner surface of theprosthesis. When the thrombi are developed to cover the inner walls ofthe synthetic vascular prostheses in a certain thickness, furtherthrombus is not formed, thus ensuring the flow of blood. Subsequently,the neointima grow whereby the synthetic vascular prosthesis acquiresthe antithrombogenic property, thus performing the function of a bloodvessel. The synthetic vascular prosthesis of this type, however, has adisadvantage that it is not applicable to a small prosthesis having aninner diameter of about less than 4mm. This is because the prosthesis isplugged by the thrombi prior to the formation of the neointimae, thuspreventing an effective patency of the prosthesis.

On the other hand, research and development have recently been made on asynthetic vascular prosthesis of the type which has an antithrombogenicproperty by itself and thus does not need the formation of theneointima. These synthetic vascular prostheses are generally dividedinto two kinds. In one kind, a living body-derived anticoagulant such asheparin, urokinase or the like is impregnated in, or is fixed throughcovalent bonds or ionic bonds to, a synthetic vascular prosthesissubstrate so as to impart the antithrombogenic property thereto. In theother kind, a hydrogel layer is formed on the inner surface of asynthetic vascular prosthesis so as to prevent direct contact between asubstrate of the prosthesis and proteinous and cellular components inthe blood, thereby acquiring the antithrombogenic property. Theprosthesis of this kind is disclosed in, for example, Japanese PatentPublication No. 60-242857.

In the former instance, however, the impregnated anticoagulant will flowaway and be lost, or if fixed, the anticoagulant will gradually lose itsactivity and efficacy. Therefore, an everlasting antithrombogenicproperty cannot be obtained.

The latter kind where the hydrogel layer is formed on the inner surfaceof the synthetic vascular prosthesis, is believed to be more suitablesince the antithrombogenic property can be maintained substantiallypermanently. Further, the synthetic vascular prosthesis of this kind isapplicable to a small-diametered portion of the blood vessel as theneointimae need not be formed.

It is known that a hydrogel layer has a good antithrombogenic propertyand is formed by graft polymerization on the inner surface of a tubularbase member which is made of elastomer, typically polyurethane. The basemember should be porous in order to render the prosthesis flexible andto facilitate a joining operation of the synthetic vascular prosthesisto a natural vessel by suture. The porous base member, however, permitsthe hydrogel to impregnate therethrough, which is not desirable becauseit promotes calcification throughout the base member and reduces theflexibility of the prosthesis. It has thus been proposed to provide athin, non-porous, dense layer between the inner surface of the basemember and the hydrogel layer, so that the hydrogel may be preventedfrom infiltrating into the base member. However, fabrication of thehydrogel layer on such a dense layer requires complicated operationssuch as plasma treatment of the inner surface of the dense layer undervacuum to generate radicals, graft polymerization of a hydrophilicmonomer (acrylamide or the like) on the inner surface, and removal ofthe resultant homopolymer not grafted. In addition, expensiveapparatuses such as a vacuum pump, a high frequency generator and thelike are necessary for the plasma treatment.

Furthermore, the provision of a dense layer increases the stiffness ofthe prosthesis and reduces the compliance. The compliance, of whichmeasurement will be described later, is a value which indicates avariation in inner capacity of the prosthesis when an internal pressureis exerted thereon. A larger value results in a larger variation in theinner capacity when the internal pressure is constant. Generally, thecompliance of the synthetic vascular prosthesis is small compared withthat of a natural blood vessel. The difference in compliance between thesynthetic vascular prosthesis and the natural vessel, tends to developan aneurysm at the joint or inosculated portion or to break theprosthesis thereat.

Accordingly, an object of the present invention is to provide asynthetic vascular prosthesis which has a satisfactory strength andcompliance as well as a good antithrombogenic property.

Another object of the invention is to provide a method for manufacturinga synthetic vascular prosthesis of the type set forth above byrelatively simple operation.

SUMMARY OF THE INVENTION

According to the invention, there is provided a synthetic vascularprosthesis which comprises a hollow tubular base member having amultitude of continuous cells or pores and formed of an elastomermaterial, and a hydrogel layer formed on the inner surface of the basemember. The outer portion of the hydrogel layer is partially embedded inthe inner portion of the base member at the pores to thereby achieveanchoring adhesion between the hydrogel layer and the base member.

This synthetic vascular prosthesis can be fabricated according to themethod of the invention which includes the steps of dissolving anelastomer material in a solvent, adding an inorganic salt to thesolution and adjusting the viscosity of the solution, subjecting thesolution to extrusion into a hollow tube, and cutting the tube to apredetermined length to form a tubular base member. After the solvent isremoved from the base member which is in turn solidified, the inorganicsalt in the inner portion of the base member is removed by dissolutionwith an acid to form a porous inner portion. A hydrogel material issubsequently coated on the inner surface of the base member so as toform a hydrogel layer on the base member, with the hydrogel materialpartially infiltrating into the pores of the porous inner portion.Thereafter, the inorganic salt in the outer portion of the base memberis removed by dissolution with an acid, thereby forming a porous outerportion having continuous pores.

Other objects, features and advantages of the invention will be apparentfrom the following detailed description thereof when taken inconjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view for use in explanation of a step for forminga porous inner portion of a tubular base member according to theinvention;

FIG. 2 is a schematic illustrative view showing how to measurecompliance; and

FIG. 3 is a schematic view showing one example of a synthetic vascularprosthesis according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

As described above, the synthetic vascular prosthesis of the inventionincludes a hollow tubular base member having a multitude of continuouspores and made of an elastomer, and a hydrogel layer formed on the innersurface of the tubular base member. The outer portion of the hydrogellayer is partially embedded in the inner portion of the base member atthe pores thereof, thereby achieving an anchoring adhesion between thehydrogel layer and the base member.

The elastomers used above include, for example, polyurethanes,polyurethane ureas, their blends with silicone polymers, siliconepolymers and other elastic polymers. In view of the durability in aliving body, the polyurethanes or polyurethane ureas are preferably ofthe polyether type and are more preferably polyether-segmentedpolyurethanes or polyether-segmented polyurethane ureas.

The hydrogel layer is preferably made of polyvinyl alcohol having adegree of polymerization of from 500 to 10,000 and degree ofsaponification of not less than 80%, or ethylene-vinyl alcoholcopolymers having a high content or vinyl alcohol. This is because thesepolymers are not dissolved in cold water and are likely to form ahydrogel, and they have a good antithrombogenic property and gooddurability.

When the hydrogel layer is partially embedded in the base member, thethickness of the embedded portion may be determined depending uponphysical properties and porosity of the elastomer material from whichthe base member is made.

In accordance with the method of the invention, the synthetic vascularprosthesis is fabricated by the steps which comprise dissolving anelastomer material in solvent, adding an inorganic salt to the resultantsolution and appropriately adjusting the viscosity of the solution to adesired level, extruding the solution into a hollow tube, and cuttingthe tube to a predetermined length to obtain a tubular base member.Thereafter, the solvent in the base member is removed and the basemember is dried for solidification, and then the inorganic salt only inthe inner portion of the base member is removed by dissolution with anacid to form an inner porous portion. A hydrogel layer is subsequentlyformed by coating a hydrogel material on the inner surface of the basemember so that the hydrogel material is partly infiltrated into thepores in the inner porous portion. Finally, the remaining, outer portionof the base member is subjected to dissolution of the inorganic salt toform an outer porous portion having continuous pores.

The elastomer material used in this method may be selected from thosementioned before. The solvents particularly for the polyether-segmentedpolyurethanes or polyether-segmented polyurethane ureas include, forexample, tetrahydrofuran, dimethylformamide, and the like.

The inorganic salts added to the solution of the elastomer material maybe any salts which are capable of dissolving out with an acid such ashydrochloric acid, sulfuric acid, acetic acid and the like. Examples ofthe salts are calcium carbonate, magnesium oxide and magnesiumhydroxide, and these salts may be used alone or in combination. In viewof the formation of the continuous pores, the amount of the salts ispreferably not less than 500 parts by weight per 100 parts by weight ofthe elastomer.

The extruder used for the extrusion process is favorably a screwextruder or a ram extruder having a circular die corresponding to theshape of the final product. Viscosity of the solution is so controlledas to adapt for the extrusion molding with these extruders by means of,for example, evaporation of the solvent.

The present invention is more particularly described below by way ofexample, in which a method of fabricating a synthetic vascularprosthesis is first described and then, the prosthesis per se isdescribed.

EXAMPLE

100 parts by weight of polyether-segmented polyurethane were dissolvedin 600 parts by weight of tetrahydrofuran to obtain a viscous polymersolution. 450 parts by weight of calcium carbonate having an averageparticle size of 1.7 micrometers and 90 parts by weight of magnesiumoxide having an average particle size of 2 micrometers were added to thesolution and kneaded, during which a part of the tetrahydrofuran wasallowed to escape by vaporization. As a result, there was obtained apaste which had a viscosity of about 1.25 g/10 minutes when measured atroom temperature by means of a melt indexer using a cylinder diameter of9.55 mm, an orifice diameter of 2.096 mm and a load of 2160 g. The pastewas supplied to a screw extruder and extruded from a circular die havinga inner diameter of 3 mm and an outer diameter of 4 mm. Whilewithdrawing with a takeup machine, the extruded product was cut into alength of about 50 to 60 cm to obtain a tubular base member A. Thetubular base member was immersed in a water tank to remove the solventfor solidification, followed by sufficient drying.

In FIG. 1, there is shown a step of forming an inner porous portion B(FIG. 3) in the inner surface of the base member A. In this step, afterthe base member A was cut at opposite ends, 3N hydrochloric acid wassupplied from a container 1 by means of a pump 2 and passed through thebase member A for about 1 minute. As a result, the calcium carbonate andmagnesium oxide which were present in the inner portion of the basemember A, were removed by dissolution in the acid to form an about 20micrometer thick inner porous portion B. Then, after the base member Awas washed with water and dried, it was held upright with one endthereof being immersed in an aqueous solution of 5% polyvinyl alcoholhaving a degree of polymerization of 1700 and a degree of saponificationof not less than 99%. The aqueous solution was then passed through thebase member A by applying a suction force to the upper end thereof, andthis sucking operation was repeated three times. The base member A wasagain dried, resulting in forming a hydrogel layer C (FIG. 3) having atotal thickness of 25 to 30 micrometers a part of which, i.e. 15 to 20micrometers thickness, was embedded in the inner porous portion B of thebase member A.

Thereafter, the tubular base member A was entirely immersed in a sealedautoclave filled with 3N hydrochloric acid and the calcium carbonate andmagnesium oxide present in the outside of the inner porous portion Bwere dissolved out under reduced pressure, thereby forming an outerporous portion D (FIG. 3) having continuous pores. After repetition ofrinsing with dilute hydrochloric acid and washing with water, the basemember was dried by a vacuum-freeze drying method at a reduced pressureof less than 2 mmHg for 12 hours in order to keep the porous condition.

The synthetic vascular prosthesis having the hydrogel layer C obtainedin this example has a section as shown in FIG. 3, with an inner diameterof about 3.00 mm and an outer diameter of 3.7 mm. The prosthesis had atthe inside thereof the hydrogel layer C, which was composed of a smoothsub-layer with a thickness of about 10 micrometers on the base member Aand an embedded sub-layer in the inner porous portion B of the basemember A with a thickness of about 15 to 20 micrometers, thus a totalthickness of the layer C being about 25 to 30 micrometers. The remainingportion of the prosthesis, i.e. the outer porous portion D, had athickness of about 320 micrometers with an average pore size of 6 to 10micrometers and porosity of about 80%.

The thus obtained synthetic vascular prosthesis of the invention feltsomewhat rigid in a dry condition because the hydrogel layer was made ofpolyvinyl alcohol. However when wetted sufficiently, the polyvinylalcohol became softened as a hydrogel (hydrous gel), exhibiting acompliance and flexibility close to those of natural blood vessels.

The compliance and flexibility were measured according to the followingmethods.

Measurement of Compliance:

The compliance is measured by a method shown in FIG. 2. A microsyringedispenser 4 is used for supplying a predetermined amount of aphysiological saline solution into a synthetic vascular prosthesis 3every operation. The variation in inner pressure of the prosthesis 3 isdetected with a pressure sensor 5 and recorded with a recorder 7 throughan amplifer 6. The compliance of the prosthesis can be obtainedaccording to the following equation (1) using the variation in innerpressure relative to the amount of the physiological saline solutioninjected into the prosthesis:

    C=V/Vo - - - - - (1)

in which V is an increment of the inner volume of the prosthesis whenthe inner pressure increases from 50 mmHg to 150 mmHg, and Vo is aninner volume of the prosthesis as an inner pressure of 50 mmHg.

Measurement of Flexibility:

The measurement of the flexibility was effected using the "Olsen" typeflexibility measuring instrument.

When the modulus of elasticity in bending of a prosthesis is taken as Eand the moment of inertia of the prosthesis is taken as I, the value EIcan be obtained by the use of the Olsen type flexibility measuringinstrument. This value was used as a standard for the flexibility.

The physical characteristics of the synthetic vascular prosthesis of theinvention determined by these methods are shown in Table 1, along with acomparative synthetic vascular prostheses which was provided with apolyether-segmented polyurethane inner layer (a dense layer) having athickness of 50 micrometers between a base member and a hydrogel.

                  TABLE 1                                                         ______________________________________                                                   C (Compliance)                                                                          Flexibility (g · cm.sup.2)                      ______________________________________                                        Comparative  0.056       2.0                                                  Example                                                                       Example of the                                                                             0.164       1.1                                                  Invention                                                                     ______________________________________                                    

As will be apparent from the foregoing, the synthetic vascularprosthesis according to the invention has a hydrogel layer having a goodantithrombogenic property, which is embedded into pores of the innerporous portion of the base member, so that an intimate bonding betweenthe hydrogel layer and the base member is ensured through anchoringadhesion. Since the hydrogel layer becomes softened in use, thecompliance and flexibility of the prosthesis of the invention are closeto those of natural blood vessels, remarkably reducing a danger ofdevelopment of an aneurysm and a breakage of the prosthesis at a suturedportion. Further, the fact that the hydrogel layer is not embedded intothe full thickness of the base member, prevents calcification and servesto maintain the flexibility of the prosthesis.

Moreover, the formation of pores in the base member according to themethod of the invention is carried out in two stages, the first stageinvolving the formation of pores only in the inner portion of the basemember. Subsequently, a hydrogel-forming material is coated on the innerportion. Thus, the formation of the pores and the coating can be carriedout relatively simply.

Although the invention has been described with reference to thepreferred embodiments thereof, many modifications and alterations may bemade within the spirit of the invention.

What is claimed is:
 1. A synthetic vascular prosthesis having acompliance close to that of a natural blood vessel, consistingessentially of:a hollow tubular base member formed of an elastomermaterial and having formed throughout a wall thereof a multitude ofcontinuous pores; and a hydrogel layer formed on the inner surface ofsaid base member, the outer portion of said hydrogel layer beingpartially embedded in the inner portion of said base member at saidpores to thereby achieve anchoring adhesion between said hydrogel layerand said base member, and said hydrogel layer having a smooth innersurface.
 2. A synthetic vascular prosthesis according to claim 1,wherein said hydrogel layer has a thickness which measures a pluralityof micrometers.
 3. A synthetic vascular prosthesis according to claim 1,wherein said hydrogel layer is formed of a material selected from thegroup consisting of polyvinyl alcohol and ethylene-vinyl alcoholcopolymers.
 4. A synthetic vascular prosthesis according to claim 3,wherein said polyvinyl alcohol has a degree of polymerization of from500 to 10,000 and a degree of saponification of not less than 80%.
 5. Asynthetic vascular prosthesis according to claim 1, wherein said basemember is formed of a material selected from the group consisting ofpolyurethanes, polyurethane ureas and silicone polymers.
 6. A syntheticvascular prosthesis according to claim 5, wherein said polyurethanes andpolyurethane ureas are of polyether type.
 7. A synthetic vascularprosthesis according to claim 6, wherein said polyether typepolyurethanes and polyurethane ureas comprise polyether-segmentedpolyurethanes and polyether-segmented polyurethane ureas, respectively.